Patent GB-947943-A (GB)
Title: Aminoalkyl-dihydroethanoanthracenes
IPC: C07C233/00
Filed: 1961-11-29
Abstract: The invention comprises 9-aminoalkyl -10R-9, 10-dihydro -9, 10-ethanoanthracenes having a nucleus of the formula: <FORM:0947943/C2/1> and acid addition salts and quaternary ammonium compounds thereof, wherein R is hydrogen or a lower alkyl group; which compounds may be further substituted in the 1- to 8-positions of the ethanoanthracene nucleus by lower alkyl, alkoxy, alkylmercapto, alkylsulphonyl or alkanoyl groups or amino, methylenedioxy or halogen substituents (the word "lower", indicating a group of 1-4 carbon atoms), with the exception of the compound 9-diethylaminomethyl -9-, 10-dihydro-9, 10-ethanoanthracene. The amino group of the 9-aminoalkyl residue may be unsubstituted or mono- or di-substituted, suitably with hydrocarbon radicals e.g. alkyl, alkenyl, cycloalkyl, cycloalkyl-alkyl, aryl or aralkyl groups or alkylene or alkenylene groups (thus forming with the nitrogen atom a heterocyclic ring), which radicals may be interrupted by hetero atoms such as oxygen, sulphur or nitrogen and/or may be substituted by free hydroxyl, amino, mercapto or halogen substituents.  The compounds are prepared by (a) converting a suitable substituent residue in the 9-position of the ethanoanthracene into the desired aminoalkyl or ammoniumalkyl group e.g. by reduction of a carbamyl, carbamylalkyl, nitroalkyl, nitroalkenyl, cyano, cyanoalkyl, acylaminoalkyl, amino-hydroxyalkyl, or aminoalkyl or hydroxyiminoalkyl group with the appropriate reducing agent; (b) introducing the 9, 10-ethano radical into the appropriate 9-aminoalkyl-anthracene or its salt or quaternary derivative, e.g. by DielsAlder reaction with ethylene; (c) introducing further substituents into the amino group of an existing primary, secondary or tertiary 9-amino-alkyl -9, 10-dihydro -9, 10-ethanoanthracene by known alkylation methods, including reductive alkylation with a carbonyl compound; or (d) treating a 9-formyl or 9-formylalkyl-dihydroethanoanthracene compound with ammonia or a primary or secondary amine followed by reduction:  9,10-Dihydro -9, 10-ethano-(1,2)-anthracene-9-aldehyde is made by Diels-Alder addition of ethylene to anthracene -9-aldehyde. N-Acetyl-9-methylaminomethyl -9, 10-dihydro -9, 10-ethano-(1, 2)-anthracene is made by acetylating the corresponding 9-methylaminomethyl compound. 9-Dimethylaminomethyl - anthracene is made by the action of dimethylamine on 9-chloromethylanthracene. b -[9, 10-Dihydro-9, 10-ethano -9-anthryl]- propionamide is made by reacting anthryl -(9)-propionic acid with ethylene converting the resulting 9, 10-dihydro -9, 10-ethano-anthryl -(9)-propionic acid to the chloride with thionyl chloride and reacting with dimethylamine. 2- or 3-Chloro-anthracene -(9)-aldehyde is made by treating 2-chloro-anthracene with phosphorus oxychloride and N-methylformamide in dichlorobenzene and adding sodium acetate. 1, 5-Dichloro -9, 10-dihydro -9, 10-ethanoanthracene -9-carboxylic acid chloride is made by reacting 1, 5-dichloroanthracene -(9)-carboxylic acid with ethylene and treating the resulting carboxylic acid with thionyl chloride.  Pharmaceutical preparations for use as tranquilizers comprise the above compounds of the invention in the free form or as their salts with organic or inorganic acids, particularly therapeutically useful acids such as salicylic, aminosalicylic or ascorbic acid, tryptophan, lysine or arginine, in admixture or conjunction with solid or liquid pharmaceutical carriers suitable for enteral (e.g. oral) or parenteral administration. The preparations suitably take the form of tablets, dragees, capsules, suspensions or emulsions, and may contain preserving, stabilising, wetting or emulsifying agents, salts for regulating osmotic pressure or buffers.  Specifications 947,945 and 947,946 are referred to.